弓形虫感染与不孕症密切相关，但具体机制不明。我们发现弓形虫排泄分泌抗原（ESA）处理人脐带间充质干细胞（hUC-MSCs）后，Cyclin A2、B1基因转录明显减少，细胞阻滞在G2/M期，p53磷酸化及促凋亡相关蛋白表达明显增加；提示p53通路可能参与ESA诱导hUC-MSCs凋亡，但ESA对胚胎干细胞（ESCs）和早期胚胎发育的影响尚未明确。体外实验发现弓形虫不能穿过小鼠早期胚胎透明带，但ESA处理可降低小鼠囊胚形成率，并上调囊胚细胞中活化半胱天冬酶-3表达及下调多能性基因Oct-4A表达，提示ESA干扰小鼠早期胚胎发育，其机制可能类似于hUC-MSCs。本项目拟用ESA处理人ESCs和小鼠早期胚胎，并建立弓形虫感染Trp53基因敲除雌鼠模型，从3个层面探讨弓形虫感染对不孕的影响及p53通路的作用。研究结果将揭示弓形虫感染引起早期胚胎发育异常及不孕症的机制，为我国优生优育计划提供借鉴。

Toxoplasma gondii (T. gondii) infection causes infertility, but the underlying mechanism is unclear. We have previously reported that T. gondii excretory secretory antigens (ESA) induced G2/M phase cell-cycle arrest and apoptosis in human umbilical cord mesenchymal stem cells (hUC-MSCs), as judged by the remarkable decreases in Cyclin A2 and Cyclin B1 transcription levels, and increased levels of phosphorylated p53 and pro-apoptotic proteins, indicating that p53 pathway might be responsible for the ESA-induced apoptosis of hUC-MSCs. However, the effects of ESA on embryonic stem cells (ESCs) and early embryonic development has not been investigated. Our previous in vitro studies revealed that although T. gondii could not penetrate the zona pellucida of mouse early embryos, ESA significantly attenuated blastocyst formation rate, elevated cleaved Caspase-3 protein levels and reduced the expression of pluripotent mediator Oct-4A in mouse blastocysts. These results suggest that T. gondii ESA interferes with early embryonic development of mice, and the underlying mechanism may be similar to that in hUC-MSCs. In the present project, by treating human ESCs and mouse early embryos with ESA, and establishing T. gondii-infected Trp53 knockout female mice models, we intend to further explore the effects of T. gondii and p53 signaling on infertility from three different aspects. The results of this study will reveal the mechanism of early embryonic dysplasia and infertility induced by T. gondii and provide useful insights for the eugenic program of our country.